PLoS One. 2014 Dec 29;9(12):e116210. doi: 10.1371/journal.pone.0116210.

A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for α9β1 integrin is involved in the anti-type II collagen antibody-induced arthritis.

Kon S1, Nakayama Y2, Matsumoto N3, Ito K2, Kanayama M2, Kimura C2, Kouro H3, Ashitomi D3, Matsuda T3, Uede T2.
  • 1Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.
  • 2Division of Molecular Immunology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
  • 3Department of Immunology, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido, Japan.

 

Abstract

Osteopontin (OPN) is a multifunctional protein that has been linked to various intractable inflammatory diseases. One way by which OPN induces inflammation is the production of various functional fragments by enzyme cleavage. It has been well appreciated that OPN is cleaved by thrombin, and/or matrix metalloproteinase-3 and -7 (MMP-3/7). Although the function of thrombin-cleaved OPN is well characterized, little is known about the function of MMP-3/7-cleaved OPN. In this study, we found a novel motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved mouse OPN binds to α9β1 integrin. Importantly, this novel motif is involved in the development of anti-type II collagen antibody-induced arthritis (CAIA). This study provides the first in vitro and in vivo evidence that OPN cleavage by MMP-3/7 is an important regulatory mechanism for CAIA.

PMID: 25545242

 

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